Functional molecular imaging of tumors by chemical exchange saturation transfer MRI of 3‐O‐Methyl‐D‐glucose

Rivlin, Michal; Tsarfaty, Ilan; Navon, Gil

doi:10.1002/mrm.25467

Cited by 73 publications

(91 citation statements)

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“…CEST MRI using D-glucose, 2-deoxy-D-glucose (2-DG), FDG, and 3-O-methy-D-glucose (3OMG) was recently shown to be useful for imaging the viable parts of tumors implanted in mice1718192021. Relative to the other CEST agents, D-glucose showed inferior sensitivity and shorter duration of the effect1920 owing to its rapid metabolism in the tumors.…”

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confidence: 99%

“…Both FDG and 2-DG enter the tumor cells through GLUT family members where they and their phosphorylated products accumulate, but they may be toxic at high concentrations. The non-metabolizable 3OMG may be a better CEST MRI alternative21, but detailed studies of its toxicity are lacking. In the present work the non-toxic GlcN and GlcNAc are tested as potential candidates for tumor imaging by CEST MRI.…”

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confidence: 99%

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Glucosamine and N-acetyl glucosamine as new CEST MRI agents for molecular imaging of tumors

Rivlin

Navon

2016

Sci Rep

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The efficacy of glucosamine (GlcN) and N-acetyl glucosamine (GlcNAc) as agents for chemical exchange saturation transfer (CEST) magnetic resonance molecular imaging of tumors is demonstrated. Both agents reflect the metabolic activity and malignancy of the tumors. The method was tested in two types of tumors implanted orthotopically in mice: 4T1 (mouse mammary cancer cells) and MCF7 (human mammary cancer cells). 4T1 is a more aggressive type of tumor than MCF7 and exhibited a larger CEST effect. Two methods of administration of the agents, intravenous (IV) and oral (PO), gave similar results. The CEST MRI observation of lung metastasis was confirmed by histology. The potential of the clinical application of CEST MRI with these agents for cancer diagnosis is strengthened by their lack of toxicity as can be indicated from their wide use as food supplements.

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Glucosamine and N-acetyl glucosamine as new CEST MRI agents for molecular imaging of tumors

Rivlin

Navon

2016

Sci Rep

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“…However, for glucose, the main drawback was associated to its rapid metabolism once entered in the tumor cells, with consequent reduction of CEST contrast capabilities. For this reason, glucose analogs, such as 2-deoxy-glucose (2DG) and 3-oxy-methyl-gluose (3OMG) have been proposed as they showed superior contrast efficiency owing to the reduced metabolic conversion in the case of 2DG (Nasrallah et al, 2013;Rivlin et al, 2013) or to the lack of metabolic transformation in the case of 3OMG (Rivlin et al, 2014). As a consequence, such derivatives provide an improved and long-lasting CEST contrast in mice carrying xenograft tumors.…”

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confidence: 98%

EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging

Longo

Moustaghfir

Zerbo

et al. 2017

International Journal of Pharmaceutics

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Chemical Exchange Saturation Transfer (CEST) approach is a novel tool within magnetic resonance imaging (MRI) that allows visualization of molecules possessing exchangeable protons with water. Many molecules, employed as excipients for the formulation of finished drug products, are endowed with hydroxyl, amine or amide protons, thus can be exploitable as MRI-CEST contrast agents. Their high safety profiles allow them to be injected at very high doses. Here we investigated the MRI-CEST properties of several excipients (ascorbic acid, sucrose, N-acetyl-d-glucosamine, meglumine and 2-pyrrolidone) and tested them as tumor-detecting agents in two different murine tumor models (breast and melanoma cancers). All the investigated molecules showed remarkable CEST contrast upon i.v. administration in the range 1-3ppm according to the type of mobile proton groups. A marked increase of CEST contrast was observed in tumor regions up to 30min post injection. The combination of marked tumor contrast enhancement and lack of toxicity make these molecules potential candidates for the diagnosis of tumors within the MRI-CEST approach.

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“…Using the recently developed LATEST method to measure CEST contrast from lactate [18], it may be possible to map the glycolytic behavior of tumors as well as probe the kinetics of LDH activity in tumor. Another glucose derivative, 3- O -methyl-glucose (3-OMG) has recently been used as an MRI contrast agent to image cancer in orthotopic xenograft of a mammary adenocarcinoma model [40]. 3-OMG is taken up rapidly and preferentially by the tumor cells and stored.…”

Section: Discussionmentioning

confidence: 99%

Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection

et al. 2017

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BackgroundImage contrast enhanced by exogenous contrast agents plays a crucial role in the early detection, characterization, and determination of the precise location of cancers. Here, we investigate the feasibility of using a non-nutritive sweetener, sucralose (commercial name, Splenda), as magnetic resonance imaging (MRI) contrast agent for cancer studies.MethodsHigh-resolution nuclear-magnetic-resonance spectroscopy and MR studies on sucralose solution phantom were performed to detect the chemical exchange saturation transfer (CEST) property of sucralose hydroxyl protons with bulk water (sucCEST). For the animal experiments, female Fisher rats (F344/NCR) were used to generate 9L-gliosarcoma model. MRI with CEST experiments were performed on anesthetized rats at 9.4 T MR scanner. Following the baseline CEST scans, sucralose solution was intravenously administered in control and tumor bearing rats. CEST acquisitions were continued during and following the administration of sucralose. Following the sucCEST, Gadolinium-diethylenetriamine pentaacetic acid was injected to perform Gd-enhanced imaging for visualizing the tumor.ResultsThe sucCEST contrast in vitro was found to correlate positively with the sucralose concentration and negatively with the pH, indicating the potential of this technique in cancer imaging. In a control animal, the CEST contrast from the brain was found to be unaffected following the administration of sucralose, demonstrating its blood–brain barrier impermeability. In a 9L glioma model, enhanced localized sucCEST contrast in the tumor region was detected while the unaffected brain region showed unaltered CEST effect implying the specificity of sucralose toward the tumorous tissue. The CEST asymmetry plots acquired from the tumor region before and after the sucralose infusion showed elevation of asymmetry at 1 ppm, pointing towards the role of sucralose in increased contrast.ConclusionsWe show the feasibility of using sucralose and sucCEST in study of preclinical models of cancer. This study paves the way for the potential development of sucralose and other sucrose derivatives as contrast agents for clinical MRI applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1221-9) contains supplementary material, which is available to authorized users.

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Functional molecular imaging of tumors by chemical exchange saturation transfer MRI of 3‐O‐Methyl‐D‐glucose

Abstract: Due to the large CEST effect of 3OMG and its low toxicity 3OMG-CEST may serve for the detection of tumors and metastases in the clinic.

Cited by 73 publications

References 24 publications

Glucosamine and N-acetyl glucosamine as new CEST MRI agents for molecular imaging of tumors

Glucosamine and N-acetyl glucosamine as new CEST MRI agents for molecular imaging of tumors

EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging

Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection

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